CTB 6 – Molecular regulation of developmental processes Flashcards
What is the difference between the development of early or late defects with respect to craniofacial malformations?
Early developmental defects cause severe craniofacial malformations which are lethal, but later are less severe which allow survival
What is holoprosencephaly?
Insufficient division of the cerebral hemispheres
What is anencephaly?
Spina bifida
How is anencephaly prevented?
Folic acid
What is the main symptom in agnathia?
Mandible not present
What is the mildest form of cleft lip?
Cleft uvula
What is the most severe form of cleft lip?
Bilateral cleft lip and palate
What is ectodermal dysplasia?
Malformation of teeth
What is the main gene involved in the spectrum of facial midline disorders, ranging from holoprosencephaly and frontonasal dysplasia? How does the gene signal in these diseases?
SHH
Loss of SHH cell signalling in holoprosencephaly
Overactivation of SHH cell signalling in frontonasal dysplasia
What genetic factors can cause impaired early embryonic developmental processes?
Mutations in development genes, chromosomal abnormalities, abnormal gene regulation
What environmental factors can cause impaired early embryonic developmental processes?
Alcohol, smoking, drugs, etc….
What is gastrulation?
3 layers (ectoderm, mesoderm, endoderm) develop and fold to form a more complex organism
What derivative in the ectoderm forms craniofacial tissues?
Neural crest
What is organogenesis?
How body plan is established
What are the 4 types of cell communication?
Endocrine
Paracrine
Neuronal
Contact-dependent
What happens to a cell if it isn’t programmed to signal?
Cell dies
What is the function of the phosphorylation cascade in cell signalling?
Induced by extracellular signal molecules to give out different cell responses
What do signalling molecules induce?
Transcription factors
What do transcription factors regulate?
Signalling molecules
Name signalling molecules.
Fgf - fibroblast growth factors
Tgfß - transforming growth factor ß
Bmp - bone morphogenic proteins
Hh - hedgehog
Name transcription factors.
Hox - homeobox Msx - muscle segment homeobox Dlx - distal-less homeobox Barx - barH-like homeobox Pax - paired box
What is the function of morphogenic gradients integrated at cellular level?
Regulate morphogenesis
What are denticles?
Tooth-like projections
Where is the opposing gradients of signalling molecules within the neural crest?
Neuroectoderm and epidermis
What are the genes in the opposing gradients of signalling molecules within the neural crest?
Overlapping gradients of BMP4 and WNT6 signalling proteins
What do the genes in the opposing gradients of signalling molecules within the neural crest induce expression of?
FoxD3 and slug
TF needed for cell specification and migration
What protein does the Hox gene encode?
DNA-binding homeodomain
What does Pax9 cause?
Oligodontia - more than 6 teeth missing
What does Pax3 cause?
Waardenburg syndrome
Where is Pax3 expressed?
Neural crest, muscle and CNS
What are the symptoms of Waardenburg syndrome?
- White hair colour
- Wide-spaced eyes (hypertenlorism)
- Short, broad nose
- Epicanthal folds
What are epicanthal folds?
Fold of the upper eyelid covering the inner corner of the eye
What basic mechanism regulates organogenesis?
Reciprocal epithelial/mescenhymal interactions
Within tooth development what happens in the initiation stage?
- Overlapping gradients of signalling molecules, FGF and BMP in the dental epithelium
- Induce transcriptional response, PAX9 and MSX1 in the dental mesenchyme
- Determines tooth position
Within tooth development what happens in the bud stage?
- Dental mesenchyme secretes signalling molecules
- Induces formation of the enamel knot (non-dividing cells) in the dental epithelium
Within tooth development what happens in the cap stage?
- Enamel knot secretes signalling molecules that induces cell cycle arrest (BMP) within enamel knot cells, but induces cell proliferation (FGF) in surrounding cells
- Determination of tooth shape
